Urotensin I (UI) and urotensin II (UII) are recently characterized neuropeptide hormones secreted by the urophysis, a neurohemal organ which is a component of the caudal neurosecretory complex (CNC) of teleost fish. The importance of these hormones resides in their structural homology with two mammalian peptide hormones. The amino acid composition of UI, a peptide consisting of about 40 residues, bears a strong resemblance to that of porcine vasoactive intestinal peptide (VIP) with which it shares a strong vasodepressor activity in mammalian and avian bioassay systems. The amino acid sequence of UII, a dodecapeptide reveals a striking homology with that of somatostatin with which it shares common physiological properties, e.g., inhibition of prolactin release by the pituitary. The immediate objectives of this research are: (1) To synthesize and purify key fragments of UI. The synthesis and purification of bioactive UII have already been accomplished in our laboratory. (2) To elicit antibodies, both classical and monoclonal, to these synthetic peptides. (3) To devise radioimmunoassays (RIA) and immunohistochemical probes using sequence-specific UI and UII antibodies. When these goals are achieved, the biochemical endocrinology of the urotensins will be investigated in collaboration with Dr. David Pearson, Division of Neurosciences, City of Hope Research Institute. These investigations will focus on the biosynthesis, bioprocessing, and release of the urotensins both in vitro in organ cultures of the CNC and in vivo under a variety of experimental conditions. These studies will provide information on the physiology and biochemical endocrinology of the neurosecretory process and will also provide the foundation for subsequent structure-activity studies of UI and UII. Because of the structural homology of UI and UII with VIP and somatostatin, respectively, such knowledge ultimately may be useful in the design of pharmacologic agents, e.g., long-acting antihypertensive peptides with minimal side effects.